While penicillin has virtually eliminated the dramatic
presentations of parenchymatous neurosyphilis, HIV, inadequate
antibiotic treatment for syphilis, and the rising incidence of early syphilis among the
young and urban poor, have increased the frequency of
subtle, atypical and often monosymptomatic presentations of neurosyphilis. These
presentations are increasingly missed as
psychiatric patients receive fewer physical exams and laboratory work-ups, physicians are
less experienced at diagnosing neurosyphilis,
and non-physicians and non-psychiatrists care for the mentally ill. Neurologic symptoms
and risks for sexually transmitted disease often
signal the presence of neurosyphilis, but the disease can present with psychiatric
symptoms alone, psychiatric symptoms that can mimic any other psychiatric illness. In this
review of literature, the authors suggest criteria for screening and stress that a
specific treponemal
test should be used because of their higher sensitivity. Treatment should consist of
penicillin plus psychotropics for any psychiatric
symptoms secondary to or concurrent with neurosyphilis. Pathogenesis, staging, clinical
presentations, and special considerations for HIV
coinfection are discussed.

The incidence of neurosyphilis, the potentially devastating infection
of the central nervous system by the spirochete Treponema
pallidum, is rising in spite of widely available curative treatment (Center for Disease
Control, 1992; Flores, 1995). Prior to the advent of
penicillin in the 1940s, the dramatic presentations of parenchymatous neurosyphilis
accounted for 20% of all admissions to psychiatric
hospitals. Today, while cases of tertiary syphilis still occur, subtle psychiatric
symptoms secondary to earlier stages of infection are much
more common. As physical exams on the mentally ill are performed less often, laboratory
screening is limited by managed care, and physicians are less experienced at diagnosing
neurosyphilis, the rises in primary and secondary syphilis of the past twenty years will
continue to translate into an increased incidence of neurosyphilis. Currently few labs use
dark field examination for early syphilis, and the most commonly used serologic tests, the
RPR and VDRL, are only 72-77% sensitive for neurosyphilis. With its complex and often
elusive
pathogenesis, neurosyphilis remains a cause of psychiatric disease.

Medical historians accept that syphilis originated in the
multinational, multiethnic mercenary army of Charles VIII of France
during his invasion of Italy in 1494. Neurosyphilis, unlike the psychiatric diseases of
antiquity like melancholia and schizophrenia,
was unknown before the last quarter of the 18th century. During the 19th century
"madness," particularly neurosyphilis, was on the rise. It
was known as the "disease of the century." Typically a young man would have sex
with a prostitute and later experience a sore on his penis or swollen inguinal lymph
nodes. This primary syphilis resolved while the spirochetes would remain in the
bloodstream. Within a year they would have invaded the meninges while remaining clinically
silent. For many years our young man would walk around symptom-free. If the immune system
could not overcome the disease, the individual might become symptomatic ten to fifteen
years later. Perhaps the aging man became unable to pronounce some kinds of phrases. Or,
less commonly, the early meningitis might have produced more frankly psychiatric symptoms
such as grandiosity characteristic of mania. As the illness advanced it primarily affected
the spinal cord causing tabes dorsalis (or locomotor ataxia), a wasting of the posterior
part of the spinal cord. Tabes would cause lancinating pains to the abdomen and
high-stepping gait called "walking on cotton." If the disease affected mainly
the brain, psychiatric symptoms would predominate, followed by dementia and paralysis
known as general paresis of the insane (G.P.I.), dementia paralytica, or progressive
paralysis. A disease primarily of middle-aged men, this was the kind most commonly
encountered in the end-stages in asylums; middle class patients were more likely to seek
relief at a spa, a resort-like treatment facility. Both tabes dorsalis and general paresis
were invariably fatal (Shorter,1997).

In 1822, Antoine-Laurent Bayle, a French physician, attributed the
psychiatric symptoms of neurosyphilis to a chronic inflammation of the meninges, and thus
made him the first to discover a psychiatric disease with definite organicity. He
established that as the underlying disease progressed, the symptoms worsened as well
(Muller, 1965). In the 1840s, potassium iodide was introduced and proved effective in the
latter stages of the disease. An epidemic of venereal disease spread across Europe and
North America in the 19th century with neurosyphilis lagging by ten to fifteen years, the
interval between the original infection and the appearance of psychiatric symptoms. There
was a reported 5 to 20% lifetime risk for syphilis in the population at that time,
(Austin, 1992) and about 6% of those would go on to develop neurosyphilis (Clark et al,
1964). By the mid-nineteenth century, advanced neurosyphilis was
treated in public asylums and private clinics. The enormous rise in frequency of
neurosyphilis explains the flood of patients into these
institutions, where paretics and tabetics constituted a large portion of the asylum
population. Not all of the afflicted were admitted to
institutions. Some died at home out of shame, others in spas or by suicide with morphine
(Flores, 1995).

In 1905 two Germans, F.R. Schaudinn and P.E. Hoffman, discovered the
causative organism which they named Spirochaeta pallida, since changed to Treponema
pallidum. In 1906-7 the Wasserman test was developed to show the presence of the disease
even when latent. The Berlin physician Paul Ehrlich in 1910 announced that
"Salvarsan," a combination of arsenic and an organic substance, blocked the
development of primary and secondary syphilis (Shorter, 1997). In 1943 John Mahoney, a
physician in the U.S. Public Health Service and Head of the Venereal Disease
Research Center on Staten Island, proved that penicillin was highly effective against
primary syphilis (Mahoney, et al, 1984). At this juncture Psychiatry lost the treatment of
syphilis to the physicians. After 1958 there was a marked decline in incidence. However in
the 1960s changes in sexual freedom probably contributed to a rise in the number of cases.
Perhaps more important than the successful pharmacologic treatment of syphilis have been
the social measures against it. The Swedes in particular have successfully tackled this
very difficult problem via model legislation involving the provision of information to the
population and voluntary anonymous testing of persons at risk. All infected individuals
must be reported and registered, but provisions of full names is not required. Contact
tracing must be performed and testing is obligatory for contacts which may be done with
the assistance of the police. Infected persons who deliberately expose others to risk may
be condemned to isolation for an unrestricted time (Cronberg, 1993).

Early syphilis includes primary, secondary, and latent syphilis.
Primary syphilis is the painless, solitary chancre that
occurs three to four weeks after infection. One-tenth to one-fourth of patients with
primary syphilis can show CSF abnormalities, most commonly a positive VDRL but also
pleocytosis and hyperglobulinemia (Moore, 1928). Patients may have an asymptomatic primary
infection or have no recollection of the primary chancre and thus do not receive
treatment. Virtually all patients with untreated primary syphilis advance to secondary
syphilis within weeks to months. Symptoms of secondary syphilis are varied and include
fever, lymphadenopathy, palmar and plantar rash, and the pathognomonic condyloma lata
mucocutaneous lesions. Patients can also have a symptomatic aseptic neurosyphilis showing
cranial nerve palsies and neuro-opthalmologic findings. Early latent syphilis occurs in
the first two years after infection when serologic markers have resolved. Patients are
asymptomatic and can be reliably diagnosed only through specific treponemal tests.
Patients with early latent syphilis frequently relapse to secondary syphilis and present
with the characteristic mucocutaneous lesions. Late latent syphilis occurs, by
conventional definition, two years after the initial infection. One-third of the untreated
patients with late latent syphilis progress to tertiary, or late, syphilis, many years
after the initial infection, while other patients remain asymptomatic indefinitely (Clark
et al, 1964). Early Syphilis can manifest as meningeal and meningovascular syphilis(see
Table 1) and has become increasingly common as number of immunocompromised patients
rise (Flores, 1995). Tertiary, or late syphilis, manifests as cardiovascular,
dermatologic, visceral, and neurologic disease.

About one-third of all patients with untreated syphilis progress to
tertiary disease. Tertiary disease is twice as common in men as women, and two to three
times more common in whites than blacks. African-Americans are more likely to develop
cardiovascular than neurologic disease (Merritt, et al, 1946). Explanations for different
rates in different groups, including gender and race, have eluded researchers. Some have
proposed the emergence of a neurotropic strain of the spirochete to explain its appearance
in the early 18th century, three hundred years after the appearance of syphilis (Hare,
1959).

TABLE 1: CLINICAL
PRESENTATIONS OF NEUROSYPHILIS (%)

Type:

Pre-antibiotic Era (Merritt, et al, 1946)

PCN era (Hotson, 1981)

Asymptomatic

31

37

Tabes

30

3

Paresis

12

8

Vascular

10

12

Meningeal

6

-

Taboparetic

3

-

Optic Neuritis/Neuro-ophthalmologic

3

17

Spinal Cord Involvement/Myelopathy

3

3

Seizures

1

18

Other

1

3

Why some neurosyphilitic patients progress and others remain
asymptomatic has remained a mystery. Investigators have documented the progression of
paretic symptoms after treponemocidal levels of antibiotics have been reached in the
central nervous system, but have not been able to explain why this occurs. What is clear
is that syphilis is acquired primarily through sexual contact, and as such, its incidence
can be dramatically reduced by the use of condoms. Transmission can also occur
transplacentally and through nonsexual human contact. Clinical Presentations of
Neurosyphilis CNS invasion by T. pallidum can occur at any stage of
syphilis (Hook, 1989), though clinically apparent disease often takes years to develop. Up
to forty percent of syphilitics show CNS involvement (Hahn, et al, 1946), and one study
estimated four to nine percent of the cases of untreated syphilitics develop symptomatic
neurosyphilis (Moore, et al, 1930). Asymptomatic patients are often discovered in routine
screenings for syphilis or in work-ups for other diseases. Symptomatic neurosyphilis is
more likely to occur with longer duration of illness, and most likely to present in white
males. Symptomatic neurosyphilis can occur at any stage of infection (Scheck, et al,
1994), and accounts for about one percent of all patients admitted to short term
psychiatric facilities in some studies (Roberts, et al, 1992).

Meningeal Syphilis is the first clinically evident presentation of
CNS involvement. It typically occurs two months to two years after the initial infection
by T. pallidum. Symptoms include headache, confusion, stiff neck, and vomiting. Patients
are afebrile and invariably have CSF abnormalities. Progression to Meningovascular
Syphilis occurs five to ten years after the initial infection, but can occur much earlier.
Patients present with focal neurologic findings secondary to multiple small infarcts due
to an endarteritis that produces hypertrophy of the intimal layer of the vasculature and
fibroblastic proliferation (Gabay, et al 1983; Lishman, 1987). CT and SPECT show multiple
cortical infarcts (Ortego, et al, 1995). Symptoms include hemiparesis, hemianopsia,
aphasia and a confusional state and are often preceded by a prodromal phase of mood
change. The onset of symptoms can be abrupt but preceded by premonitory symptoms of
headache, dizziness, insomnia, memory loss and mood disturbances that can last weeks to
months. Psychiatric symptoms including personality and behavioral change, and slowing of
mentation and speech may present similarly (Merritt, et al 1946; Holmes et al, 1984) to
paresis.

The diagnosis of meningovascular neurosyphilis should be considered
in young patients presenting with symptoms of a cerebrovascular accident. The differential
diagnosis of meningovascular syphilis includes lacunar strokes secondary to hypertension,
atherosclerotic vascular disease, cerebral emboli and cerebral vasculitis (Swartz, 1990).
Meningovascular syphilis is still relatively common.(see Table 1).

Parenchymatous Neurosyphilis, including Tabes, meaning wasting, and
Paresis, from the Greek word meaning 'relaxation,' occurs ten to twenty years after the
initial infection. It has become rare in the post-antibiotic era but anecdotal reports
still make note of its existence (Giles, 1980; Hoffman, 1982; Fitchtner, et al, 1991).
Patients may also present with taboparesis, a combined form of the two (Lishman, 1987).

Paresis involves the general deterioration of mental and physical
capabilities. Symptoms typically begin ten to fifteen years after the initial infection
and include memory loss, impaired concentration and ability to learn, irritability, mania,
depression, and psychosis. Its insidious onset can mimic any neurologic or psychiatric
illness. Neurologic symptoms include a lack of facial expression, or paralyzed facies,
tremors of the lips, tongue, facial muscles, and fingers, and impaired handwriting and
speech (Swartz, 1990). Late psychiatric symptoms are predominated by a dementia
indistinguishable from other forms of dementia, including impaired judgment, confusion and
lack of insight (Dawson-Butterworth, et al, 1970).

Confirming a diagnosis of paresis can be accomplished through
laboratory testing(see Table 1). Though treatable, it has a poor prognosis for recovery of
function because of diffuse neuronal loss (Merritt, et al, 1946). Paresis most commonly
occurs in the fourth through sixth decades of life (Dewhurst, 1969).
Tabes, occurring 15-25 years after infection, has the longest latency period and is
exceedingly rare in the post-Antibiotic era(see Table 2). Symptoms begin with sensory loss
and progress to lightning pains secondary to atrophy and fibrosis of muscle nerve roots,
wasting, Argyll Robertson pupils, a positive Romberg sign, and diminished deep tendon
reflexes. Ataxia predominates the later symptoms (Scheck, et al, 1994). Lower extremity
pain secondary to tabes is described as shooting, in contrast to pain secondary to pain
due to diabetic and other peripheral neuropathies, which is often described as burning
(Swartz, 1990).

The diagnosis of neurosyphilis on laboratory data alone is
difficult, if not impossible. Patients may have abnormal CSF values without neurosyphilis
and conversely, neurosyphilis without abnormal CSF findings. Diagnosis requires using
several tests in addition to clinical findings. Laboratory tests for syphilis include
non-treponemal and specific treponemal tests. Specific treponemal tests include
fluorescent treponemal antibody absorption (FTA) and Treponema pallidum hemagluttinin
(TPHA). FTA involves incubating a patient's serum on a slide coated with dead T.p., then
adding fluorescent tagged antibodies to human antibodies.

TPHA, also referred to as Microhemagglutination for Treponema
pallidum(MHA-TP), uses sheep erythrocytes coated with T.p. antigens that agglutinate in
the presence of serum exposed to T.p. Specific tests have a sensitivity between 97% and
100%, but remain positive even after successful treatment. Thus FTA or TPHA can be used
alone as an effective screening test to rule out neurosyphilis. Retrospective studies have
shown that ten percent of patients with a positive serum TPHA have CNS involvement
(Roberts, et al, 1992). CSF-FTA may not be useful because of the high number of false
positives (Simon, 1985).

Non-treponemal tests include the Venereal Disease Research
Laboratory (VDRL) test and the rapid plasma reagin (RPR), which are less sensitive than
FTA and TPHA. VDRL uses an antigen composed of cardiolipin, cholesterol, and lecithin that
is cross reactive with T.p. antigens to precipitate antibodies to T.p. The RPR is a
similar test that uses carbon particles as the antigen, and since its introduction in
1976, has largely replaced the VDRL. Non-treponemal CSF exam remains the best method for
confirming a diagnosis of neurosyphilis. Non-treponemal tests are, however, unsuitable for
screening of neurosyphilis because their sensitivity is between thirty and seventy percent
in latent and late syphilis and because twenty-five percent of patients with latent
syphilis may revert to negative VDRL within two years (Hart, 1986). Dementia is due to
late disease and thus a non-treponemal test is more likely to be falsely negative.
Additionally, prior antibiotic treatment for other infections can eliminate serologic VDRL
markers while leaving CNS treponemal involvement intact (Dijkstra, 1983). Though some of
the historically low sensitivity of non-treponemal tests may reflect the erroneous
over-diagnosis of "seronegative neurosyphilis," specific treponemal tests should
be used preferentially for screening (Flores, 1995). Non-treponemal CSF exam is the
diagnostic test of choice in follow-up. Rising titers, as indicated by an increase in the
dilutional number, may signify continued disease (Roberts, 1995).
Patients with a non-reactive CSF-VDRL who present with other signs of neurosyphilis,
including atypical neurologic or psychiatric symptoms, a prior history of Syphilis, and a
positive specific serum test, warrant an expanded work-up (Vartdal, et al, 1982). An
intrathecal Treponema pallidum antibody (ITPA) index has been used for increased
specificity (Gachnait, et al, 1981). CSF polymerase chain reaction (PCR) is an expensive
test that does not provide additional benefit in diagnosing neurosyphilis (Marra, et al,
1996).

Controversy has surrounded the issue of routine screening for
neurosyphilis in patients presenting with new onset neurologic or psychiatric symptoms.
Several studies have argued that routine screening is an important part of work-ups for
new onset psychosis, mania, depression, and dementia (Wijesurendra, et al, 1992; Roberts,
et al, 1992; Mlisana, et al, 1992; Bell, 1959) while others have argued that the cost of
screening outweighs the rare cases of neurosyphilis that are discovered (Banks, 1968).

One study presented seventeen patients with neurosyphilis, of which
only six were diagnosed correctly at initial presentation. The remaining eleven patients
were referred to nine different departments before the correct diagnosis of neurosyphilis
was made (Luxon et al, 1979). Numerous anecdotal reports present cases of misdiagnosis of
neurosyphilis and the resulting increase in cost and morbidity (Allen, et al, 1983;
Sivakumar, et al, 1992; Hoffman, 1981). As the mentally ill are increasingly cared for by
non-physicians and non-psychiatrists, at peripheral or community care centers, and in
managed care institutions, physical exams and laboratory work-ups are performed much less
frequently (Hoffman, 1981). The incidence of syphilis and neurosyphilis are rising as
subtle neurologic findings on physical exam and serologic markers are missed or
overlooked. Patients with a history of psychiatric illness have an increased incidence of
sexually transmitted disease and are more likely to be misdiagnosed than are
non-psychiatric patients. The physical complaints of psychiatric patients are often
neglected, as other medical care-givers label their presentations as purely
"psychiatric" (Leeman, 1975). In addition, psychiatric patients are often
unaware of or unable to communicate their medical illnesses (Hall, et al, 1982). As a
result, greater than forty percent of patients presenting to psychiatric clinics have
underlying medical illness, and between ten and twenty percent of these have a medical
illness contributing to their symptomatology (Koranyi, 1979).

As clinical presentations of neurosyphilis have changed in the last
fifty years, the demographics of the disease have changed as well (Hutchinson, et al,
1991; Hamill, et al, 1989). Sub-therapeutic antibiotic therapy has arrested a large number
of cases in latent disease and virtually eliminated parenchymal neurosyphilis in the
elderly. In contrast, the rise in intravenous drug abuse, oral contraceptives and
promiscuity among youths have contributed to the rise of syphilis in younger patients. The
incidence of early syphilis is also rising dramatically in urban centers, in adolescent
and adult females, and in populations with high rates of social disruption (Rolfs, et al,
1990). Syphilis, like other sexually transmitted diseases, is increasing in inner-city
minority populations(Anonymous, 1988). One study found that the prevalence of syphilis was
increased in women in urban centers who had not sought prenatal care, and inferred that
patients like them, with little knowledge of sexually transmitted disease, less access to
health care, and young age, had a higher chance of contracting syphilis and other sexually
transmitted diseases (Mlisana, et al, 1992).

Homosexual males, though still at increased risk, have modified
their sexual practices in response to the AIDS threat, and thus have contracted fewer
cases of syphilis. Though the incidence of neurosyphilis is changing among different
groups, risk factors remain the same as for other sexually transmitted diseases. Drug
usage, active male homosexuality, unprotected sex, and prostitution are all contributing
to the rise in early syphilis and thus the increased incidence of neurosyphilis. Factors
that should raise suspicion include a negative family history of mental illness (Gomez, et
al, 1984), risk factors for sexually transmitted disease, neurologic symptoms and an
organic component to the mental status exam. A history of syphilis, either treated or
untreated, HIV, and pre-existing mental illness (Kalichman, et al, 1994; Coverdale, 1995;
Kelly, et al, 1995) are the most important risk factors in the development of
neurosyphilis.

What is clear is that any patient presenting with neurologic or
psychiatric symptoms and risk factors for sexually transmitted diseases should be screened
for neurosyphilis (Farshy, et al, 1986). Patients with severe and chronic mental illness,
including schizophrenia, bipolar disorder, dementia and psychotic depression should alert
the clinician to the possibility of neurosyphilis because of their risks for sexually
transmitted disease. Cournos, et al., 1994 and Kalichman, et al., 1994 have documented the
alarming frequency of high-risk sexual activity in the chronically mentally ill
population, often in the context of drug or alcohol use.56,60 One set of screening
guidelines is that of O'Neil and McCaffrey, who recommend selective screening for syphilis
based on risks and clinical presentations. (SeeTable 3)61 Psychiatric history and a
history of poor medical care should also be considered in testing psychiatric patients for
neurosyphilis. As serum FTA is nearly 100% sensitive in all stages of the disease and
costs the provider between $7-19, it is thus the screening test of choice. If positive, a
lumbar puncture for CSF cell count and VDRL should be performed (Roberts, et al, 1992). A
diagnosis of neurosyphilis is made if there is CSF pleocytosis (> 5 cells/mm3) and a
positive CSF-VDRL or neurologic symptoms with a negative CSF-VDRL. Additionally, family
members and sexual contacts of a patient with neurosyphilis should receive serologic
screening (Rundell, et al, 1995).

The presentation of psychiatric symptoms due to neurosyphilis is
often identical to psychiatric presentations secondary to any other etiology, and
neurosyphilis can present as any psychiatric symptom.

Unlike the striking clinical presentations of parenchymatous
neurosyphilis that were common prior to antibiotic therapy, presentations have become
subtle and atypical. Dementia, depression and grandiosity are currently the most common
psychiatric presentations. Auditory hallucinations listed as the most common psychotic
symptom in an article publishe in 1905 (Craig, 1905). One study implicated neurosyphilis
as the causative agent in three of 268 cases of schizophrenia (Johnstone, et al, 1987).
With the high prevalence of psychiatric disease in the general population and the
relatively low incidence of neurosyphilis, it is likely that a significant number of
psychiatric patients also have neurosyphilis contributing in varying amounts to their
condition. Neurosyphilis can alter the course of pre-existing psychiatric illness.
Frequency of psychotic episodes in schizophrenics can increase, response to treatment can
decrease, and organic involvement can cloud consciousness (Sivakumar, et al, 1992).
Psychosomatic presentations of neurosyphilis must also be considered. Subtle findings on
physical exam or vague complaints in a patient's history when accompanied by histrionic,
grandiose, or irritable personality change are easily misdiagnosed as somatoform disorders
(Rundell, et al, 1995). Neurosyphilis has also been misdiagnosed as chronic alcoholism.
Paretic alcoholics were misdiagnosed with Korsakoff's psychosis or dementia (Lishman,
1987). Even before the use of antibiotics, psychiatric presentations were changing. In the
late 19th and early 20th centuries, well before the advent of penicillin, dementia
replaced grandiosity as the most common psychiatric presentation of neurosyphilis.

Hare suggests that the Upper Classes were more likely to experience
delusions of wealth and grandeur, and since its spread to the population at large,
dementia and depression have become the most common psychiatric manifestations (Hare,
1959).

Neurologic symptoms in a new onset illness should raise the
possibility of neurosyphilis. Neurosyphilis often presents with both psychiatric and
neurologic symptoms. Common symptoms include decreased tendon reflexes (76% with reflex
change, 67% with absent ankle jerk, 5% with Babinski sign), seizures, and
neuro-opthalmologic findings (45% with pupillary abnormality, 12% with
chorioretinitis/retinary pigmentosa, and 5% with optic atrophy). Thirty-four percent have
a sensory abnormality (Hooshmand, et al, 1972). Transient neurologic symptoms including
aphasias, parasthesias, sensory deficits, headaches, ataxia, or symptoms of
cerebrovascular events should raise suspicion of neurosyphilis. Adults with new onset
partial seizures of unknown etiology, whether remaining focal or with secondary
generalization, should be screened for neurosyphilis (Hotson, 1981). It is also possible
that neurosyphilis can increase susceptibility to other neurologic diseases (Wilner, et
al, 1968).

Standard treatment of neurosyphilis is aqueous penicillin G.
Alternative regimens of Amoxicillin and Ceftriaxone have been used successfully but their
efficacy has not been documented in large scale studies (Tramont, 1976; Mohr, et al,
1976). HIV positive patients may need higher doses of PCN and additional follow-up. The
Jarisch-Herxheimer reaction of fever and aggravation of syphilitic symptoms, including
exacerbation of psychosis and development of seizures, can follow the initiation of
therapy (Hahn, et al, 1958). It occurs more commonly in early Syphilis but can occur in 2%
of paretics who undergo treatment. The reaction, thought to be caused by the release of
products from dead spirochetes, can affect long term outcome in parenchymal infection,
particularly when in the optic and auditory nerves (Idsoe, et al, 1976). Tabetic sensory
complaints secondary to fibrosis and atrophy of dorsal roots and posterior columns may
fail to resolve with penicillin therapy. Lightning pains can be treated with carbamazepine
(Ekborn, 1972).

Psychiatric symptoms due to neurosyphilis should be addressed in the
same manner as the psychiatric illnesses they mimic. Certain caution should be observed in
that patients with neurosyphilis may be more susceptible to the side effects of
psychotropics. Cannon and Sperry reported the case of a patient with neuroleptic malignant
syndrome and suggested that neurosyphilis acted as a cofactor in the initiation of the
reaction.

Electroconvulsive therapy (ECT) may be contra-indicated because the
temporary disruption of the blood brain barrier that it causes may allow an increased
involvement of the parenchyma by spirochetes (Dewhurst, 1969), but reports have been
inconclusive (Dewhurst, 1969). Another report suggested that ECT was effective in the
treatment of a patient refractory to medical treatment (Weaver, et al, 1982). Physical and
occupational therapy, as well as psychotherapy, may be beneficial in re-integrating a
patient back into his normal life (Cannon, et al, 1992). Response to
therapy occurs more rapidly with shorter duration of both infection and neurologic disease
(Brown, et al, 1985). Successful treatment is defined as a normalization of CSF cell count
in six months and a fourfold drop in CSF-VDRL titers. Diligent follow-up is needed in
patients with neurosyphilis.

One study showed that at least 31% of patients who had been treated
for paresis showed progression of neurologic disease after ten years (Bordon, et al,
1985). Other reports have presented treatment failures in spite of recommended dosages of
penicillin therapy (Dijkstra, 1983; Tramont, 1976; Gimenez-Roldan, et al, 1979). Patients
should receive lumbar punctures every six months for two years. CSF-VDRL remains the best
diagnostic test to monitor recurrence of the disease. IV PCN is the drug of choice in
treatment failures, and though no guidelines have been made, higher dosages are needed for
cases resistant to treatment (Mohr, et al, 1976). In a five year
follow-up of patients with neurosyphilis, 50% of patients showed resolution of
disorientation, convulsions, tremors, incontinence, euphoria and depression, while only
25% of patients showed resolution in delusions, hallucinations, and impaired memory,
judgment, speech, and calculations. Mild or early cases predictably have a greater chance
in showing resolution of symptoms. Patients with active disease, as evidenced by CSF
pleocytosis, were more likely to respond to treatment than were patients with static
pathology without CSF pleocytosis (Lishman, 1987). Men are more likely to be confused
after ten to fifteen years, while women are more often dysarthric and depressed
(Dawson-Butterworth, et al, 1970).

Several recent studies have shown the existence of high coinfection
rates between syphilis and HIV (Hutchinson, et al, 1991; Bordon, et al, 1985; Quinn, et
al, 1990, Musher, et al, 1990; Katz, et al, 1989; Dowell, et al, 1992; Lukehart, et al,
1988; Schofer, 1996; Katz, et al, 1993), and subsequent alterations in the natural course
of neurosyphilis. It has been suggested that a specific relationship between HIV and
neurosyphilis exists (Johns, et al, 1987; Tramont, 1987; Spence, et al, 1987,; Hook,
1989). One study of 4863 STD patients revealed 24% of those with syphilis to be HIV
positive compared to 3.5% of those without syphilis (Quin, et al, 1990). Another study
showed that 44% of neurosyphilis patients had AIDS. Coinfection patients are more likely
to be younger and present with more CSF abnormalities, syphilitic meningitis,
ophthalmologic findings and a larger variety of neurosyphilis (Katz, et al, 1989). Half of
HIV positive asymptomatic patients with serologic markers for syphilis may have
neurosyphilis (Dowell, et al, 1992), in contrast to 10% of HIV negative patients. A
patient with HIV, serologic markers for syphilis and CSF pleocytosis should be diagnosed
with neurosyphilis even in the absence of symptoms or CSF-VDRL reactivity (Musher, et al,
1990). Presentation of HIV and syphilis coinfection is even more likely to be atypical
than other presentations of neurosyphilis (Radolf, et al, 1988). HIV causes treatment
failures and relapses after treatment. It also causes early neurosyphilis to occur
frequently, especially after conventional penicillin therapy (Musher, et al, 1990).
Patients with HIV need more aggressive work-ups, treatment and follow-up for
neurosyphilis.

Neurosyphilis has not become a disease relegated to historical
interest. One study attributed 1.3% of the admissions to a short-term psychiatric unit to
neurosyphilis (Roberts, et al, 1992), while a much higher incidence of asymptomatic
neurosyphilis in psychiatric patients exists. The dramatic presentations of tabes and
paresis have been replaced by subtle, atypical findings that are more likely to be missed
as clinicians are less experienced in diagnosing the disease, managed care facilities
limit the availability of routine testing, and non-MDs care for the mentally ill. Syphilis
remains the "great imitator," only now our ability to accurately diagnose
patients is markedly compromised. Patients presenting with risk factors for sexually
transmitted disease and subtle neurologic or psychiatric symptoms should receive a
serologic screening with a specific treponemal test, and if positive, lumbar puncture for
CSF-VDRL and cell count. Though the likelihood of discovering new cases of neurosyphilis
through routine screening is statistically small, the clinical significance of a twenty
dollar test cannot be overstated because of the disease's response to treatment and
potentially devastating outcome if not addressed. Patients with HIV and syphilis
coinfection warrant aggressive work-ups and treatment. All patients should be followed-up
with lumbar punctures every six months for two years. Perhaps because of the dramatic drop
in the incidence of neurosyphilis since the advent of penicillin, fewer researchers have
focused on the disease than other organic diseases causing psychiatric illness.
Researchers have been unable to explain how neurosyphilis, like HIV, can cause such a
wide-spectrum of seemingly unpredictable clinical presentations. There exists the
possibility that a new epidemic of syphilis could translate into large numbers of patients
with potentially devastating CNS infection. This risk is particularly high in the
chronically mentally ill. Research on the treatment of psychiatric symptoms independent of
penicillin therapy is lacking. Neurosyphilis has played a profound role in the development
of psychiatry as the first psychiatric disease for which an organic etiology was found.
Today, as neuropsychiatrists are grappling with the complex presentations and reemergence
of the disease as new diagnostic modalities and mind-brain paradigms emerge, psychiatrists
are challenged with diagnosing neurosyphilis with only subtle clinical findings in their
new found roles as "primary care" physicians and serving as consultants on
neurosyphilis patients treated by other physicians.

32. Hahn RD, Webster B, Weickhardt G, Thomas E,
Timerblake W, Solomon H. The Results of Treatment in 1086 General Paralytics, The Majority
of Whome were Followed for More Than Five Years. J Chronic Dis. 1958;7:209-227

47. Johns DR, Tierney M, Felsenstein D. Alteration
in the Natural History of Neurosyphilis by Concurrent Infection with the Human
Immunodeficiency Virus. New England Journal of Medicine. 1987;316:1569-1572

48. Johnstone EC, MacMillan R, Crow TJ. The
Occurrence of Organic Disease of Possible or Probable Aetiological Significance in a
Population of 268 Cases of First Episode Schizophrenia. Psychol Med. 1987;17:371-379